Reifenstein Syndrome

At a glance

A syndrome characterized by hypogonadism as a result of a defect in androgen receptor. Often described as the male pseudohermaphrodism, presenting with hypospadias, gynecomastia, normal XY karyotype, and a pattern X-linked recessive inheritance.

Synonyms

Partial Androgen Insensitivity; Gynecomastia-Hypospadias Syndrome; Hereditary Familial Hypogonadism; Male Pseudohermaphroditism; Gilbert-Dreyfus Syndrome; Lubs Syndrome.

Classification

Two types have been suggested:

• Type I: Refers to the familial incomplete male pseudohermaphrodism.

• Type II: Autosomal recessive.

Incidence

Estimated in up to 1/20,000 live births

Genetic inheritance

X-linked recessive.

Pathophysiology

Underlying defect is the partial deficiency of androgen receptors (AR), causing partial androgen resistance, and not because of a lack of androgen synthesis.

Diagnosis

Clinical features (hypogonadism); family history; elevated plasma luteinizing hormone and testosterone levels; oligospermia or azoospermia; testis biopsy show normal Leydig and Sertoli cells but immature germinal cells and no spermatozoa; cultured fibroblast from genital skin show reduced levels of androgen receptor present with decreased cytoplasmic dihydrotestosterone binding capacity. The normal chromosomal study (46,XY) and normal testosterone conversion enzyme study (particularly 5-reductase level) exclude other causes of androgen resistance.

Clinical aspects

The phenotype is quite variable as a consequence of the partial sensitivity of the androgen receptors. In its mildest form, the man is infertile but otherwise normal. In its most severe form, the male pseudohermaphrodite may have hypospadias, cryptorchism, bifid scrotum, microphallus, atrophic ectopic testes, pseudovagina, gynecomastia, and absent vas deferens. Axillary and pubic hair is usually normal but chest and facial hair are minimal. Temporal recession of hairline is minimal and the voice is prepubertal in character. Azoospermia is common and occasionally accompanied by hypoplasia of vas deferens. Most have a male psychological development. Germ cell malignancies can occur.

Anesthetic considerations

There are no reported considerations for this disorder. However, supplemental steroid administration perioperatively might be indicated.

Other conditions to be considered

• 17-Beta Hydroxysteroid Dehydrogenase Deficiency (17-Ketosteroid Reductase Deficiency; 17-Beta HSD Syndrome): Presents clinically as male pseudohermaphroditism associated with significant enlargement of the adrenal glands and production of steroids impaired. It is inherited as either autosomal recessive or X-linked recessive.

• 17-Alpha Hydroxylase Deficiency: Presents clinically in adolescence because of failure of the adrenal gland and testes to produce androgens. Because males are not exposed to androgens during fetal development they are born with female external genitalia. Failure to menstruate or to develop secondary sexual traits such as breasts or body hair, hypertension, and hypokalemia are characteristics.

• 3-Beta Hydroxysteroid Dehydrogenase Deficiency (3-Beta-HSD): Presents clinically at birth and leads to death within the first few hours. Glucocorticoids and mineralocorticoids are not ...